TY - JOUR
T1 - Prospective early response imaging biomarker for neoadjuvant breast cancer chemotherapy
AU - Lee, Kuei C.
AU - Moffat, Bradford A.
AU - Schott, Anne F.
AU - Layman, Rachel
AU - Ellingworth, Steven
AU - Juliar, Rebecca
AU - Khan, Amjad P.
AU - Helvie, Mark
AU - Meyer, Charles R.
AU - Chenevert, Thomas L.
AU - Rehemtulla, Alnawaz
AU - Ross, Brian D.
PY - 2007/1/15
Y1 - 2007/1/15
N2 - Purpose: The American Cancer Society estimates that in 2006, 212,920 women will be diagnosed with breast cancer and that 40,970 women will die from the disease. The development of more efficacious chemotherapies has improved outcomes, but the rapid assessment of clinical benefit from these agents remains challenging. In breast cancer patients receiving neoadjuvant chemotherapy, treatment response is traditionally assessed by physical examination and volumetric-based measurements, which are subjective and require macroscopic changes in tumor morphology. In this study, we evaluate the feasibility of using diffusion magnetic resonance imaging (MRI) as a reliable and quantitative measure for the early assessment of response in a breast cancer model. Experimental Design: Mice implanted with human breast cancer (MX-1) were treated with cyclophosphamide and evaluated using diffusion MRI and growth kinetics. Histologic analyses using terminal nucleotidyl transferase - mediated nick end labeling and H & E were done on tumor samples for correlation with imaging results. Results: Cyclophosphamide treatment resulted in a significant reduction in tumor volumes compared with controls. The mean apparent diffusion change for treated tumors at days 4 and 7 posttreatment was 44 ± 5% and 94 ± 7%, respectively, which was statistically greater (P < 0.05) than the control tumors at the same time intervals. The median time-to-progression for control and treated groups was 11 and 32 days, respectively (P < 0.05). Conclusion: Diffusion MRI was shown to detect early changes in the tumor microenvironment, which correlated with standard measures of tumor response as well as overall outcome. Moreover, these findings show the feasibility of using diffusion MRI for assessing treatment response of a breast tumor model in a neoadjuvant setting.
AB - Purpose: The American Cancer Society estimates that in 2006, 212,920 women will be diagnosed with breast cancer and that 40,970 women will die from the disease. The development of more efficacious chemotherapies has improved outcomes, but the rapid assessment of clinical benefit from these agents remains challenging. In breast cancer patients receiving neoadjuvant chemotherapy, treatment response is traditionally assessed by physical examination and volumetric-based measurements, which are subjective and require macroscopic changes in tumor morphology. In this study, we evaluate the feasibility of using diffusion magnetic resonance imaging (MRI) as a reliable and quantitative measure for the early assessment of response in a breast cancer model. Experimental Design: Mice implanted with human breast cancer (MX-1) were treated with cyclophosphamide and evaluated using diffusion MRI and growth kinetics. Histologic analyses using terminal nucleotidyl transferase - mediated nick end labeling and H & E were done on tumor samples for correlation with imaging results. Results: Cyclophosphamide treatment resulted in a significant reduction in tumor volumes compared with controls. The mean apparent diffusion change for treated tumors at days 4 and 7 posttreatment was 44 ± 5% and 94 ± 7%, respectively, which was statistically greater (P < 0.05) than the control tumors at the same time intervals. The median time-to-progression for control and treated groups was 11 and 32 days, respectively (P < 0.05). Conclusion: Diffusion MRI was shown to detect early changes in the tumor microenvironment, which correlated with standard measures of tumor response as well as overall outcome. Moreover, these findings show the feasibility of using diffusion MRI for assessing treatment response of a breast tumor model in a neoadjuvant setting.
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U2 - 10.1158/1078-0432.CCR-06-1888
DO - 10.1158/1078-0432.CCR-06-1888
M3 - Article
C2 - 17255264
AN - SCOPUS:33846883993
SN - 1078-0432
VL - 13
SP - 443
EP - 450
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 2 I
ER -